Hypoxia - Inducible Factor - 1 α in Pulmonary Artery Smooth Muscle Cells Lowers Vascular Tone by Decreasing Myosin Light Chain Phosphorylation Short Communication

Organismal survival requires cells to sense and respond to changes in oxygen tension. Hypoxia-inducible factor1α (HIF-1α), an oxygen (O 2 )–sensitive transcription factor, facilitates cellular responses to hypoxia by regulating genes involved in angiogenesis, oxygen transport, and energy metabolism. The pulmonary vasculature responds to hypoxia with vasoconstriction and remodeling; however, the role of HIF-1α in the pulmonary circulation remains unclear. Sustained hypoxic exposure results in pulmonary hypertension, a disease characterized by pulmonary artery (PA) vasoconstriction and neomuscularization. In a murine model, haploinsufficiency of HIF-1α attenuates hypoxia-induced increases in PA pressure, right ventricular hypertrophy, and pulmonary vascular remodeling, suggesting that HIF-1α might play a role in increasing pulmonary vascular tone. However, recent data in PA smooth muscle cells (PASMCs) indicate that HIF-1α regulates the expression of an ion channel subunit that mitigates vasoconstriction. Insight into the role that HIF1α plays in modulating pulmonary vascular tone and in the pathogenesis of pulmonary hypertension is limited, in part, by neonatal lethality in mice lacking HIF-1α. Thus, to test the hypothesis that PASMC HIF-1α modulates both basal PA tone and the response to hypoxia, we created mice with an SMCspecific deletion of HIF-1α.